1.Humanizing NOD/SCID/IL-2Rγnull (NSG) mice using busulfan and retro-orbital injection of umbilical cord blood-derived CD34+ cells.
Young Kyung KANG ; Yunmi KO ; Aery CHOI ; Hyeong Jwa CHOI ; Jin Hee SEO ; Minyoung LEE ; Jun Ah LEE
Blood Research 2016;51(1):31-36
BACKGROUND: Humanized mouse models are still under development, and various protocols exist to improve human cell engraftment and function. METHODS: Fourteen NOD/SCID/IL-2Rγnull (NSG) mice (4‒5 wk old) were conditioned with busulfan and injected with human umbilical cord blood (hUCB)-derived CD34+ hematopoietic stem cells (HSC) via retro-orbital sinuses. The bone marrow (BM), spleen, and peripheral blood (PB) were analyzed 8 and 12 weeks after HSC transplantation. RESULTS: Most of the NSG mice tolerated the regimen well. The percentage of hCD45+ and CD19+ cells rose significantly in a time-dependent manner. The median percentage of hCD45+cells in the BM was 55.5% at week 8, and 67.2% at week 12. The median percentage of hCD45+ cells in the spleen at weeks 8 and 12 was 42% and 51%, respectively. The median percentage of hCD19+ cells in BM at weeks 8 and 12 was 21.5% and 39%, respectively (P=0.04). Similarly, the median percentage of hCD19+ cells in the spleen at weeks 8 and 12 was 10% and 24%, respectively (P=0.04). The percentage of hCD19+ B cells in PB was 23% at week 12. At week 8, hCD3+ T cells were barely detectable, while hCD7+ was detected in the BM and spleen. The percentage of hCD3+ T cells was 2‒3% at week 12 in the BM, spleen, and PB of humanized NSG mice. CONCLUSION: We adopted a simplified protocol for establishing humanized NSG mice. We observed a higher engraftment rate of human CD45+ cells than earlier studies without any significant toxicity. And human CD45+ cell engraftment at week 8 was comparable to that of week 12.
Animals
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B-Lymphocytes
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Bone Marrow
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Busulfan*
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Fetal Blood
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Hematopoietic Stem Cells
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Humans*
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Mice*
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Spleen
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T-Lymphocytes
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Umbilical Cord*
2.Real-World Efficacy Data and Predictive Clinical Parameters for Treatment Outcomes in Advanced Esophageal Squamous Cell Carcinoma Treated with Immune Checkpoint Inhibitors
Jwa Hoon KIM ; Bokyung AHN ; Seung-Mo HONG ; Hwoon-Yong JUNG ; Do Hoon KIM ; Kee Don CHOI ; Ji Yong AHN ; Jeong Hoon LEE ; Hee Kyoung NA ; Jong Hoon KIM ; Yong-Hee KIM ; Hyeong Ryul KIM ; Hyun Joo LEE ; Sung-Bae KIM ; Sook Ryun PARK
Cancer Research and Treatment 2022;54(2):505-516
Purpose:
This study aimed to evaluate the real-world efficacy of immune checkpoint inhibitors (ICIs), and to identify clinicolaboratory factors to predict treatment outcomes in patients with advanced esophageal squamous cell carcinoma (ESCC) receiving ICIs.
Materials and Methods:
Sixty patients with metastatic or unresectable ESCC treated with nivolumab (n=48) or pembrolizumab (n=12) as ≥ second-line treatment between 2016 and 2019 at Asan Medical Center were included.
Results:
The median age of the patients was 68 years (range, 52 to 76 years), and 93.3% were male. Most patients had metastatic disease (81.7%) and had been previously treated with fluoropyrimidines, platinum, and taxane. In 53 patients with measurable disease, the overall response rate and disease control rate were 15.1% and 35.8%, respectively. With a median follow-up duration of 16.0 months, the median progression-free survival (PFS) and overall survival (OS) were 1.9 months (95% confidence interval [CI], 1.54 to 2.19) and 6.4 months (95% CI, 4.77 to 8.11), respectively. After multivariate analysis, recent use of antibiotics, low prognostic nutrition index (< 35.93), high Glasgow Prognosis Score (≥ 1) at baseline, and ≥ 1.4-fold increase in neutrophil-to-lymphocyte ratio after one cycle from baseline were significantly unfavorable factors for both PFS and OS. Younger age (< 65 years) was a significant factor for unfavorable PFS and hyponatremia (< 135 mmol/L) for unfavorable OS.
Conclusion
The use of ICIs after the failure of chemotherapy showed comparable efficacy in patients with advanced ESCC in real practice; this may be associated with host immune-nutritional status, which could be predicted by clinical and routine laboratory factors.